Gene expression changes induced by SMPD1 or GPR64 silencing in A673 Ewing Sarcoma cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE252963 | GEO | 2024/09/25
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression changes induced by SMPD1 or GPR64 silencing in A673 Ewing Sarcoma cells
| PRJNA1063324 | ENA
Project description:EWS-FLI-1 was silenced by an shRNA in A673 Ewing sarcoma cells and the resulting alterations in the secretome was analyzed by GeLC-MS/MS approach (six gel slices for each sample, luciferase shRNA-expressing cell secretome as control)
2021-07-06 | PXD016052 | Pride
Project description:STAG2, a member of cohesin, is one of the most recurrently mutated genes in human cancer. Here, we investigated STAG2 function in the context of Ewing sarcoma, an aggressive bone tumor driven by EWS-FLI1 oncogene chimeric transcription factor. A673 Ewing sarcoma cell line was trasfected with siCT or 2 different siRNA targetting STAG2 during 72h and CTCF HiChIP experiments were preformed for each conditions. Analyses of HiChIP data show that STAG2 knowck-down alters CTCF-anchored loop extrusion.
2021-04-29 | GSE156650 | GEO
Project description:As the second most common malignant bone tumor in children and adolescents, Ewing sarcoma is initiated and exacerbated by a chimeric oncoprotein, most commonly, EWS-FLI1. In this study, we apply epigenomic analysis to characterize the transcription dysregulation in this cancer, focusing on the investigation of super-enhancer and its associated transcriptional regulatory mechanisms. We demonstrate that super-enhancer-associated transcripts are significantly enriched in EWS-FLI1 target genes, contribute to the aberrant transcriptional network of the disease, and mediate the exceptional sensitivity of Ewing sarcoma to transcriptional inhibition. Through integrative analysis, we identify MEIS1 as a super-enhancer-driven oncogene, which co-operates with EWS-FLI1 in transcriptional regulation, and plays a key pro-survival role in Ewing sarcoma. Moreover, APCDD1, another super-enhancer-associated gene, acting as a downstream target of both MEIS1 and EWS-FLI1, is also characterized as a novel tumor-promoting factor in this malignancy. These data delineate super-enhancer-mediated transcriptional deregulation in Ewing sarcoma, and uncover numerous candidate oncogenes which can be exploited for further understanding of the molecular pathogenesis for this disease.
2018-12-04 | GSE117485 | GEO
Project description:The molecular hallmark of the Ewing family of tumors is the presence of balanced chromosomal translocations leading to the formation of chimerical transcription factors (i.e. EWS/FLI1) that play a pivotal role in the pathogenesis of Ewing tumors by deregulating gene expression. We have recently demonstrated that DAX1 (NR0B1), an orphan nuclear receptor which was not previously implicated in cancer, is induced by the EWS/FLI1 oncoprotein and is highly expressed in Ewing tumors, suggesting that DAX1 is a biologically relevant target of EWS/FLI1-mediated oncogenesis. In this work we demonstrate that DAX1 is a direct transcriptional target of the EWS/FLI1 oncoprotein through its binding to a GGA-rich region in the DAX1 promoter and show that DAX1 is a key player of EWS/FLI1-mediated oncogenesis. DAX1 silencing using an inducible model of RNA interference induces growth arrest in the A673 Ewing cell line and severely impairs its capability to grow in semisolid medium and form tumors in immunodeficient mice. Gene expression profile analysis demonstrated that about ten percent of the genes regulated by EWS/FLI1 in Ewing cells are DAX1 targets, confirming the importance of DAX1 in Ewing oncogenesis. These findings indicate that DAX1 is an important player in the pathogenesis of the Ewing family of tumors, identify new functions for DAX1 as a cell cycle progression regulator and open the possibility to new therapeutic approaches based on DAX1 function interference. A673 cells derived from Ewing sarcoma were genetically enginereed to express specific shRNAs against GFP (control), EWS/FLI1 and DAX1 upon doxycycline stimulation. Three independent clones and a polyclonal population from each enginereed cell were analyzed. Cells were stimulated with doxycycline for 72 hours to induce the expression of the corresponding shRNA and whole gene expression profile performed. Gene expression profile in A673 cells in which EWS/FLI1 or DAX1 were silenced were compared to the control cells.
2012-02-23 | E-GEOD-36007 | biostudies-arrayexpress
Project description:Polycomb proteins are essential regulators of gene expression in stem cells and development. They function to reversibly repress gene transcription via posttranslational modification of histones and chromatin compaction. In many human cancers, genes that are repressed by polycomb in stem cells are subject to more stable silencing via DNA methylation of promoter CpG islands. Ewing sarcoma is an aggressive bone and soft-tissue tumor that is characterized by overexpression of polycomb proteins. This study investigates the DNA methylation status of polycomb target gene promoters in Ewing sarcoma tumors and cell lines and observes that the promoters of differentiation genes are frequent targets of CpG-island DNA methylation. In addition, the promoters of ion channel genes are highly differentially methylated in Ewing sarcoma compared with nonmalignant adult tissues. Ion channels regulate a variety of biologic processes, including proliferation, and dysfunction of these channels contributes to tumor pathogenesis. In particular, reduced expression of the voltage-gated Kv1.5 channel has been implicated in tumor progression. These data show that DNA methylation of the KCNA5 promoter contributes to stable epigenetic silencing of the Kv1.5 channel. This epigenetic repression is reversed by exposure to the DNA methylation inhibitor decitabine, which inhibits Ewing sarcoma cell proliferation through mechanisms that include restoration of the Kv1.5 channel function.This study demonstrates that promoters of ion channels are aberrantly methylated in Ewing sarcoma and that epigenetic silencing of KCNA5 contributes to tumor cell proliferation, thus providing further evidence of the importance of ion channel dysregulation to tumorigenesis.
| S-EPMC4716008 | biostudies-literature
Project description:Gene expression changes induced by SFRP2 silencing in RB383 retinoblastoma cells
| PRJNA680275 | ENA
Project description:Rhabdomyosarcoma (RMS) is a malignant tumor that represents the most common form of pediatric soft tissue sarcoma. It arises from mesenchymal origin and forms part of the group of small round blue cell tumors of childhood. It has a constant annual incidence of 4.5 cases per 1,000,000 children. The known histological diagnosis of the two major subtypes (embryonal and alveolar) has been recently enhanced by tumor biological markers and molecular differentiation diagnostic tools that have improved not only the updated classification based on risk stratification, but also the treatment approach based on the clinical group. Ewing sarcoma (ES) is a round cell tumor, highly malignant and poorly differentiated that is currently the second most common malignant bone tumor in children. In rare instances, it develops from an extraskeletal origin, classified as extraosseous Ewing sarcoma (EES). We provide an updated, evidence-based and comprehensive review of the molecular diagnosis, clinical and diagnostic approach and a multidisciplinary medical and surgical management according to the latest standard of care for the treatment of pediatric RMS and EES.
| S-EPMC6306718 | biostudies-other
Project description:Poly(ADP-ribose) polymerase 1 (PARP1) critically facilitates DNA damage response (DDR) that suppresses genomic instability. However, the physiological function of PARP1 in regulating genomic integrity is unclear. We investigated the Ewing’s sarcoma breakpoint region 1 (EWS) and found that it regulated the physiological function of PARP1. EWS was indispensable to dissociation of PARP1 from damaged DNA, promoting DDR and regulating DDR protein expression. Abnormal PARP1 accumulation due to EWS expression silencing, induced hyper-PARylation, which exhausted cellular NAD+ levels and caused cell death in in vitro and in vivo. Positively charged EWS arginine-glycine-glycine (Arg-Gly-Gly, RGG) domains directly interact with poly ADP-ribose (PAR) chains produced by PARP1 and are essential to dissociate PARP1 from damaged DNA. Consistently, Ewing’s sarcoma cells with defective EWS function accumulated PARP1 on chromatin and tissues from Ewing’s sarcoma patients, exhibiting high PARylation levels. Taken together, loss of EWS causes defects in PARP1 dissociation and results in genomic instability.
2020-11-03 | PXD016145 | Pride
Project description:The molecular hallmark of the Ewing family of tumors is the presence of balanced chromosomal translocations leading to the formation of chimerical transcription factors (i.e. EWS/FLI1) that play a pivotal role in the pathogenesis of Ewing tumors by deregulating gene expression. We have recently demonstrated that DAX1 (NR0B1), an orphan nuclear receptor which was not previously implicated in cancer, is induced by the EWS/FLI1 oncoprotein and is highly expressed in Ewing tumors, suggesting that DAX1 is a biologically relevant target of EWS/FLI1-mediated oncogenesis. In this work we demonstrate that DAX1 is a direct transcriptional target of the EWS/FLI1 oncoprotein through its binding to a GGA-rich region in the DAX1 promoter and show that DAX1 is a key player of EWS/FLI1-mediated oncogenesis. DAX1 silencing using an inducible model of RNA interference induces growth arrest in the A673 Ewing cell line and severely impairs its capability to grow in semisolid medium and form tumors in immunodeficient mice. Gene expression profile analysis demonstrated that about ten percent of the genes regulated by EWS/FLI1 in Ewing cells are DAX1 targets, confirming the importance of DAX1 in Ewing oncogenesis. These findings indicate that DAX1 is an important player in the pathogenesis of the Ewing family of tumors, identify new functions for DAX1 as a cell cycle progression regulator and open the possibility to new therapeutic approaches based on DAX1 function interference.
2012-02-23 | GSE36007 | GEO